Diabetes is widely believed to be caused by abnormality in two hormones, that is, absolute or relative insulin deficiency and relative glucagon excess. Insulin deficiency results in defects in sugar utilization, whereas glucagon excess leads to excessive production of sugar. Both cases contribute to hyperglycemia of diabetic patients.
Accordingly, inhibition of glucagon action is a rational method for reducing the blood sugar level of diabetic patients. Theoretically, glucagon action can be inhibited by reducing glucagon levels in the blood or by antagonizing glucagon action in the liver. The former can be achieved by suppressing the production or secretion of glucagon from a cells, or by neutralizing glucagon in the circulating blood. The latter can be achieved by administration of an effective glucagon receptor antagonist (NPL 1). Various low-molecular-weight glucagon receptor antagonists have been proposed so far, and they are reportedly able to reduce the blood sugar level of diabetic animal models. However, no compounds have been clinically used until now, and the development of compounds with higher drug efficacy and safety has been expected. For example, compounds (BAY 27-9955: NPL 2; and NMC 25-0926: NPL 3) shown below are reported as glucagon receptor antagonists; however, none of them has a 2-furancarboxylic acid hydrazide structure; their structures are different from the structure of the compound of the present invention.

In contrast, the following compound is referred to as an example of a compound having a 2-furancarboxylic acid hydrazide structure (PTL 1).
    wherein A is a group represented by Formula (a) below:
                wherein either R4 or R5 is a cyano group, a nitro group, or the like, and the other is a hydrogen atom or a halogen atom,or the like;            either R1 or R2 is a group: -D-(X)m-R6, an aryl group, or the like, and the other is a group: -E-(Y)n-R7, a hydrogen atom, an aryl group, or the like;    R3 is a hydrogen atom, a halogen atom, or the like;    D and E are the same or different, and independently represent an arylene group;    X and Y are the same or different, and independently represent —O—, —S—, —SO—, —SO2—, —OSO2—, —NR8—, —CO—, —CH═CH—, —C≡C—, —CONH—, —NHCO—, —NHCOO—, —OCH2CONH—, or —OCH2CO—;    R6 and R7 are the same or different, and independently represent a C1-10 alkyl group, an aryl C1-4 alkyl group, a heteroaryl C1-4 alkyl group, or the like, with the alkyl moiety of the aryl C1-4 alkyl group or heteroaryl C1-4 alkyl group being optionally substituted with hydroxy;    R8 is a hydrogen atom or a C1-10 alkylcarbonyl group; and    m and n are independently 0 or 1;    provided that the aryl group, the aryl moiety, the heteroaryl group, the heteroaryl moiety, and the arylene group are optionally substituted with 1 to 4 atoms or groups selected from the group consisting of halogen, hydroxy, etc.
PTL 1 discloses a number of compounds in detail. However, only the following five compounds are disclosed as 2-furancarboxylic acid hydrazide derivatives having an aminophenyl group in position 3 of the furan ring.

These compounds (Compounds A to E) all have a 3-aminophenyl group as a partial structure. PTL 1 neither specifically discloses compounds having a 4-aminophenyl group as their partial structures, nor suggests their structures. In contrast, the glucagon receptor antagonistic activity of the 2-furancarboxylic acid hydrazide derivative disclosed in PTL 1 is not satisfactory at all. The creation of compounds having more potent antagonistic activity has been desired.